Human amylin aggregates release within exosomes as a protective mechanism in pancreatic β cells : Pancreatic β-hippocampal cell communication
Copyright © 2021 The Author(s). Published by Elsevier B.V. All rights reserved..
Pancreatic β cells are essential in the maintenance of glucose homeostasis during the progression to type 2 Diabetes Mellitus (T2DM), generating compensatory hyperinsulinemia to counteract insulin resistance. It is well known, that throughout the process there is an increased mTORC1 signaling pathway, with an impairment in different quality control systems including ubiquitin-proteasome system and autophagy. In addition, under this situation, pancreatic β cells start to accumulate amylin protein (IAPP) in aggregates, and this accumulation contributes to the failure of autophagy, damaging different organelles such as plasma membrane, endoplasmic reticulum, mitochondria, and others. Here, we report that IAPP can be incorporated to multivesicular bodies (MVB) and secreted into exosomes, a mechanism responsible for the exportation of these toxic aggregates as vehicles of cell to cell communication. On this regard, we have demonstrated that the exosomes bearing toxic hIAPP released from pancreatic β cells are capable to induce hyperactivation of mTORC1 signaling, a failure in the autophagic cellular quality control, and favor pro-fission status of the mitochondrial dynamics in hippocampal cells. In summary, our results show that harmful accumulation of hIAPP in pancreatic β cells may be detoxified by the release of exosomes, which may be captured by endocytosis mechanism damaging neuronal hippocampal cells, which suggest an underlying molecular mechanism to the link between type 2 diabetes and neurodegenerative diseases.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2021 |
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| Erschienen: |
2021 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:1868 |
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| Enthalten in: |
Biochimica et biophysica acta. Molecular cell research - 1868(2021), 5 vom: 09. Apr., Seite 118971 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Burillo, J [VerfasserIn] |
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Aggregates |
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| Anmerkungen: |
Date Completed 17.09.2021 Date Revised 17.09.2021 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1016/j.bbamcr.2021.118971 |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM320770486 |
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| 245 | 1 | 0 | |a Human amylin aggregates release within exosomes as a protective mechanism in pancreatic β cells |b Pancreatic β-hippocampal cell communication |
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| 520 | |a Copyright © 2021 The Author(s). Published by Elsevier B.V. All rights reserved. | ||
| 520 | |a Pancreatic β cells are essential in the maintenance of glucose homeostasis during the progression to type 2 Diabetes Mellitus (T2DM), generating compensatory hyperinsulinemia to counteract insulin resistance. It is well known, that throughout the process there is an increased mTORC1 signaling pathway, with an impairment in different quality control systems including ubiquitin-proteasome system and autophagy. In addition, under this situation, pancreatic β cells start to accumulate amylin protein (IAPP) in aggregates, and this accumulation contributes to the failure of autophagy, damaging different organelles such as plasma membrane, endoplasmic reticulum, mitochondria, and others. Here, we report that IAPP can be incorporated to multivesicular bodies (MVB) and secreted into exosomes, a mechanism responsible for the exportation of these toxic aggregates as vehicles of cell to cell communication. On this regard, we have demonstrated that the exosomes bearing toxic hIAPP released from pancreatic β cells are capable to induce hyperactivation of mTORC1 signaling, a failure in the autophagic cellular quality control, and favor pro-fission status of the mitochondrial dynamics in hippocampal cells. In summary, our results show that harmful accumulation of hIAPP in pancreatic β cells may be detoxified by the release of exosomes, which may be captured by endocytosis mechanism damaging neuronal hippocampal cells, which suggest an underlying molecular mechanism to the link between type 2 diabetes and neurodegenerative diseases | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a Aggregates | |
| 650 | 4 | |a Amylin | |
| 650 | 4 | |a Diabetes | |
| 650 | 4 | |a Exosomes | |
| 650 | 4 | |a MVB | |
| 650 | 4 | |a Mitochondrial dynamics | |
| 650 | 7 | |a Islet Amyloid Polypeptide |2 NLM | |
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| 700 | 1 | |a Fernández-Rhodes, M |e verfasserin |4 aut | |
| 700 | 1 | |a Piquero, M |e verfasserin |4 aut | |
| 700 | 1 | |a López-Alvarado, P |e verfasserin |4 aut | |
| 700 | 1 | |a Menéndez, J C |e verfasserin |4 aut | |
| 700 | 1 | |a Jiménez, B |e verfasserin |4 aut | |
| 700 | 1 | |a González-Blanco, C |e verfasserin |4 aut | |
| 700 | 1 | |a Marqués, P |e verfasserin |4 aut | |
| 700 | 1 | |a Guillén, C |e verfasserin |4 aut | |
| 700 | 1 | |a Benito, M |e verfasserin |4 aut | |
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